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Nagelhout Video 2- Exam 1 Flashcards

1
Q

Succinylcholine structure

A

two ACh molecules stuck together

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2
Q

Succinylcholine broken down by

A

plasma cholinesterase

First broken down into:
succinyl-monocholine and choline

Then into
Succinic acid and choline

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3
Q

What is recycled to make new Ach?

A

Choline

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4
Q

What partof sux metabolism is metabolized via the kreb’s cycle?

A

succinic acid

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5
Q

Why does succinylcholine have such a brief duration?

A

rapid hydrolysis in plasma by cholinesterase enzyme to inactive metabolites

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6
Q

all the cholinesterases do the SAME thing which is-

A

break things down via hydrolysis - by adding water

MOST UBIQUITOUS ENZYME IN THE BODY

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7
Q

What are the cholinesterase family of enzymes?

A

hydrolytic enzymes that hydrolyze ACh and ester LAs at the synaptic cleft more quickly than others at other conditions

-allows for proper nerve signalling by preventing overstimulation

names for this family :
acetylcholinesterase (synapse of muscles)
pseudocholinesterase (plasma)

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8
Q

ESTERASE ENZYMES -

2 types of CHOLINESTERASE

A

Acetylcholinesterase (muscle synapse)

Pseudocholinesterase (plasma)

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9
Q

ESTERASE ENZYMES -

Non-specific esterases

A

RBC esterase

Paraxonase

Albumin Esterase

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10
Q

Common esterase dependent anesthesia drugs - Pseudocholinesterase (PChE)

A

Succinylcholine

Mivacurium

Ester local anesthetics (cocaine, procaine, chloroprocaine, tetracaine)

Neostingmine

Edrophonium

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11
Q

Common esterase dependent anesthesia drugs - Non-specific esterases (plasma)

A

Atracurium
Cisatracurium
Remifentanil
Clevidipine

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12
Q

Common esterase dependent anesthesia drugs - RBC esterases

A

Esmolol

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13
Q

Some people have atypical cholinesterase in their bodies what does this mean?

A

Will result in different metabolization rates of succinylcholine and ester LAs

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14
Q

Is atypical cholinesterase a pathologic condition?

A

No its an inherent difference among human beings- most common is Homozygote A (EaEa)
-tested via Dibucaine test

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15
Q

atypical cholinesterase - Homozygote A decreases enzyme activity by

A

> /= 70%, prolongs effects for 4-24 hours

Results in a Dibucaine test number of 16-30

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16
Q

Which test is used to determine if a person is slow to metabolize succinylcholine due to atypical cholinesterase?

A

DIBUCAINE INHIBITION TEST

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17
Q

What is dibucaine?

A

An amide local anesthetic which inhibits typical or usual pseudocholinesterase (PchE) but not atypical

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18
Q

Normal dibucaine number

A

80

Means that 80% of the ACh-esterase activity was inhibited by dibucaine

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19
Q

If dibucaine number is 20

A

the patient has an atypical enzyme since dibucaine did not inhibit the patient’s enzyme activity

20
Q

If a patient experiences prolonged apnea following succinylcholine or mivacurium administration what must you differentiate between?

A

Atypical genetic variant of AChE or just low levels of AChE enzyme
-via Dibucaine test

21
Q

Low dibucaine number + normal activity =

A

atypical enzyme and prolonged apnea

22
Q

Normal dibucaine number + low activity =

A

Normal enzyme with low levels present and prolonged apnea

23
Q

Normal dibucaine number + normal activity =

A

normal enzyme and amount (another reason for prolonged apnea must be investigated)

24
Q

Low dibucaine number + Low activity =

A

atypical enzyme with low levels present and prolonged apnea

25
Q

PChE variant - usual

Homozygote U (EuEu)

A

96% frequency

Normal enzyme activity

Duration of Succinylcholine is normal

Dibucaine test number- 70-80

26
Q

PChE variant - Atypical

Homozygote A (EaEa)

A

0.3% frequency

Decreased enzyme activity by >/= 70%

Duration of succinylcholine is SIGNIFICANTLY prolonged 4-24 hours

Dibucaine number is 16-30

27
Q

Succinylcholine side effects

A

Hyperkalemia
Dysrhythmias- hyperK related
Myalgia- from fasciculations
Myoglobinemia
Elevated intragastric pressure
Elevated IOP
Elevated ICP-from fasciculations and high CVP
MH
Masseter Spasm-followed by MH sometimes

28
Q

Succinylcholine side effects - Hyperkalemia

A

Normally serum K+ increased by 0.5 mEq/L secondary to potassium leaking from the depolarized muscle

In patients with crush injuries, burns, denerving injuries, MH, K+ levels are much higher

29
Q

Succinylcholine side effects- Dysrhythmias

A

From hyperK or ganglionic effects of succinylcholine

-Wide EKG complexed leading to arrest have been seen in children with dystrophin-deficient muscular dystrophies (duchennes, becker)

30
Q

Succinylcholine side effects - Myalgia

A

Secondary to fasciculation even though some patients complain of muscle pain without having shown evidence of fasciculation

31
Q

Succinylcholine side effects - Myoglobinemia

A

Rare complication after extensive fasciculation or MH

32
Q

Succinylcholine side effects - elevated intragastric pressure

A

can occur from contractions of ab muscles d/t fasciculation

The elevation of intragastric pressure seen with succinylcholine are less significant than occur with CO2 insufflation during laparoscopic surgery

33
Q

Succinylcholine side effects - Increase IOP

A

Ketamine + succinylcholine do this

-MOA unknown - seems related to contraction of ocular muscles during fasciculation from sux

34
Q

Succinylcholine side effects - Malignant hypothermia

A

genetic predisposition

-MOA of succinylcholine triggering this is poorly understood

35
Q

Succinylcholine side effects - masseter spasm

A

More often in kids than adults. Can be early sign of MH

so when succinylcholine is used with halothane vs when used with thiopental

36
Q

Which patients is succinylcholine contraindicated in?

A

patients at risk for upregulation of ACh receptors

Ex-
· Upper or lower motor neuron defect
· Prolonged chemical denervation (i.e.) muscle relaxants, magnesium, clostridial toxins)
· Direct muscle trauma, tumor, or inflammation
· Thermal trauma/ Burns=
· Disuse atrophy
· Severe infection

37
Q

Contraindications to succinylcholine

A

Hyperkalemia / hyperkalemia d/t renal failure (not the renal failure itself but the high K+

Burn patients -35% TBSA - 3rd degree

Severe muscle trauma

Neuro injury - paraplegia / quadplegia

Severe sepsis (abdominal)

Muscle wasting/ prolonged immobilization

MH

Denervating diseases

Duchenne muscular dystrophy- why we don’t give succinylcholine to kids; DMD can be undetected

Selected muscle disorders - in general patients with muscle disease shouldn’t receive

Children under 8 years old - only emergency situations (airway-kids don’t show typical signs of issues)

Genetic variants of pseudocholinesterase

Stains - (?) per nagelhout - ok

Allergy

38
Q

Patients with muscle disease & succinylcholine

A

avoid sux
-patients with muscle disease will have increased sensitivity to non-depolarizing muscle relaxants and have lower dose requirements too

39
Q

Cholinesterase enzymes:
Acetylcholinesterase (AChE)

A

known as true, specific, genuine, type 1

membrane bound glycoprotein

40
Q

Cholinesterase enzymes:
Pseudocholinesterase (PChE)

A

known as plasma, serum, benzoyl, false, butryl, nonspecific, type 2

-has over 11 isoenzyme variants

41
Q

Cholinesterase enzymes:
Pseudocholinesterase (PChE) locations

A

plasma
liver
smooth musc
intestine
pancreas
heart
white matter

42
Q

Cholinesterase enzymes:
Acetylcholinesterase (AChE) locations

A

erythrocytes
nerve endings
lungs
spleen
gray matter

43
Q

Neostigmine elimination half life

A

70-80 min

It takes 70-80 mins to eliminate the Ne Yo song stuck in my head

44
Q

Edrophonium elimination half life

A

110 min - healthy pt
300 min - impaired renal function pt

-75% excreted by kindeys

45
Q

Which do you give first, AChE inhibitor or anticholinergic/antimuscarinic?

A

Anticholinergic 1st

want to prevent the negative effects of the AChE inhibitor first

-could give neostigmine and robinul at same time technically

advanced pharm 2 for na (14 decks)

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